Transamidation

Transamidation, also called amide exchange, is a chemical reaction in which an amide bond is transferred between two components, typically a carboxamide and an amine, to give a new amide and a leaving amine. It represents an acyl-transfer process in which the substituents attached to the amide nitrogen are exchanged.

Mechanistically, transamidation requires activation of the relatively inert amide carbonyl. Reactions are often promoted by acid or base catalysis, or by transition-metal catalysts, and may proceed via activation of the amide or via a more reactive derivative such as an activated ester. The incoming amine attacks the carbonyl carbon to form a tetrahedral intermediate, followed by expulsion of the original amine as the leaving group. The efficiency and selectivity depend on the nature of the amide (primary or secondary amides are generally more reactive than tertiary ones) and the nucleophilicity and leaving ability of the amine substituents.

Scope and considerations: Transamidation applies to a broad range of aliphatic and aromatic amides and amines. Equilibrium control is important, as amide exchange can be reversible; reactions are often driven by removing the expelled amine or using excess incoming amine, catalysts, or activating conditions. Solvent, temperature, and functional-group tolerance also influence outcomes, and hydrolysis or side reactions can limit practicality under some conditions.

Applications and context: Transamidation is used in organic synthesis to modify amide-containing substrates, in medicinal chemistry to alter drug-like molecules, and in polymer or peptide chemistry for selective amide modification or remodeling. It complements direct amidation and aminolysis as a tool for amide bond manipulation.